asymmetric autocatalysis triggered by carbon isotope (13c
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Asymmetric Autocatalysis Triggered by Carbon Isotope (13C/12C) Chirality
Hong Ren 06-19-09
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Asymmetric Autocatalysis Triggered by Carbon Isotope (13C/12C) Chirality
Hong Ren 06-19-09
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Asymmetric Autocatalysis Triggered by Carbon Isotope (13C/12C) Chirality
Hong Ren 06-19-09
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
The Homochirality Remains a Puzzle…
Hong Ren @ Wulff Group
The Homochirality Remains a Puzzle…
Hong Ren @ Wulff Group
All the 20 natural amino acids are left-handed.
1st step Shattering the mirror: Absolute Asymmetric Synthesis
2nd step Propagating the imbalance: Asymmetric Autocatalysis
A proposed theory to explain the origin of the homochirality:
Blackmond, D. G. PNAS, 2004, 101, 5732-5736.
Asymmetric Autocatalysis and Its Implications for the Chemical Origin of Life
Hong Ren @ Wulff Group
N
N
OH2
ZnN
N
OZn H N
N
OH
N
N
CHO
+
2
Zn
with low enantiomeric enrichment
with hign enantiomeric enrichment
Soai, K.; Shibata, T.; Morioka, H.; Choji, K. Nature, 1995, 378, 767-768.
Asymmetric Autocatalysis Triggered by Carbon Isotope (13C/12C) Chirality
Hong Ren 06-19-09
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Generation of Chirality by Carbon Isotope Substitution
Hong Ren @ Wulff Group
12C C12
X Y
Achiral compound
12C C13
X Y
carbon isotope substitution
Isotopic enantiomers
Solution: Asymmetric Autocatalysis
Problem: Experimentally inaccessible: very small difference between 13C and 12C
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Discrimination of the Carbon Isotopic Chirality by Asymmetric Autocatalysis
Hong Ren @ Wulff Group
H3C
Ph OH
13CH3
13C
13C13C
13C
C1313C
H OH
(R)-1 (S)-3
H313CO OCH3
H OH
(S)-2
H313C CH3
Ph OH
H OH
(S)-1 (R)-3
H3CO O13CH3
H OH
(R)-2
13C
13C13C
13C
C1313C
Carbon Isotopic Enantiomers
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Hong Ren @ Wulff Group
Discrimination of the Carbon Isotopic Chirality by Asymmetric Autocatalysis
N
N
CHO
+
4
2
Zn
N
N
OZn N
N
OZn
tiny ee tiny ee
asymmetric autocatalysis
asymmetric autocatalysis
4+ i-Pr2Zn 4+ i-Pr2Zn
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Hong Ren @ Wulff Group
N
N
OH
(S)
N
N
OH
(R)
Enhancement of Enantiomeric Excess
Highly Enantioenriched (S)-5 Highly Enantioenriched (R)-5
Discrimination of the Carbon Isotopic Chirality by Asymmetric Autocatalysis
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Synthesis of Compound 1---Route 1
Hong Ren @ Wulff Group
Ph
O
13CH3
+ Me2Zn H3C
Ph OH
13CH3
(R)-1, 89% ee
H313C CH3
Ph OH
(S)-1, 93% ee
Ph
O
CH3
+ (13CH3)2Zn
ligand (-)-8
NH
NH
SHO2
SO2
OH
OH
Ti(Oi-Pr)4, toluene
Ti(Oi-Pr)4, toluene
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Hong Ren @ Wulff Group
Synthesis of Compound 1---Route 2
Ph
13CH2
OH
CO2i-PrHO
HO CO2i-Pr
DIPT
Ti(Oi-Pr)4, t-BuOOH,DCM
PhOH
H213C O
1) p-toluenesulfonic anhydride, DMAP, pyridine
2) LAH, ether
H3C
Ph OH
13CH3
(R)-1, 86% ee
H313C CH3
Ph OH
(S)-1, 90% ee
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Hong Ren @ Wulff Group
O
OCH3Na, 13CH3OH H3
13CO OCH3
H OH
(S)-2
1) Ph3P, diisopropyl azodicarboxylate,
p-NO2C6H4COOH, THF
2) K2CO3, MeOH
H3CO O13CH3
H OH
(R)-2
Na, 13CH3OH
O
OCH3
Synthesis of Compound 2
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Synthesis of Compound 3
13C6H5CHO
N
CH3OH
PhPh
(p-Br)C6H4B(OH)2diethylzinc, toluene
13C
13C13C
13C
C1313C
H OH
(S)-3, 96% ee
H OH
(R)-3, 99% ee
13C
13C13C
13C
C1313C
Br
Br
1) TMSCl, TEA, THF2) n-BuLi, B(OEt)3, THF3) diethylzinc, toluene then H2O4) TBAF, THF
13C
13C13C
13C
C1313C
H OH
(S)-3, 96% ee
H OH
(R)-3, 99% ee
13C
13C13C
13C
C1313C
+
Hong Ren @ Wulff Group Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K.
Science, 2009, 324, 492.
Entry Chiral alcohol Isolated yield ee configurition 1 (R)-1 (89% ee) 94 92 S 2 (S)-1 (93% ee) 95 96 R 3 (R)-1 (89% ee) 80 88 S 4 (S)-1 (93% ee) 94 96 R 5 (R)-1 (89% ee) 96 88 S 6 (S)-1 (93% ee) 97 94 R 7 (R)-1 (89% ee) ND 93 S 8 (S)-1 (93% ee) 92 93 R
Hong Ren @ Wulff Group
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Chiral Discrimination of the Isotopic Carbons Using Compound 1 from Route 1
Entry Chiral alcohol Isolated yield ee configurition 1 (R)-1 (86% ee) 94 94 S 2 (S)-1 (86% ee) 87 95 R 3 (R)-1 (86% ee) 93 94 S 4 (S)-1 (90% ee) 98 93 R 5 (R)-1 (86% ee) 85 92 S 6 (S)-1 (84% ee) 93 88 R 7 (R)-1 (86% ee) 88 89 S 8 (S)-1 (90% ee) 93 90 R
Hong Ren @ Wulff Group
Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science, 2009, 324, 492.
Chiral Discrimination of the Isotopic Carbons Using Compound 1 from Route 2
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